With few exceptions, carcinogens are mutagenic agents that react with and damage DNA. Various physical and chemical agents are known to induce cancer in humans, such as UV-irradiation and vinyl chloride. About 80 percent of all human cancer may be caused by environmental chemical substances, both man-made and naturally occurring. In recent years, a number of short-term microbial mutagenesis assays have been developed for the detection of chemical mutagens. The most widely used and probably the most reliable microbial mutagenesis test is the Salmonella/mammalian-microsome reverse mutation assay. The test was significantly improved by the introduction of plasmid pKM101 in some of the tester strains. However, the test still does not detect certain classes of carcinogens. The objective of the proposed research is to screen a large number of plasmids to find ones that will be superior to pKM101 or that will supplement pKM101 by making one or more tester strains responsive to known or suspected carcinogens not detected by the test in its present form. Making the test more sensitive will enhance its predictive value for human carcinogenicity induced by environmental mutagens.